Interference of mouse mammary tumor virus replication by PTT.119 [p-fluoro-L-phe-m-bis-(2-chloroethyl)amino-L-phe-met ethoxy HCl]--an antitumor agent.

Abstract

PTT.119 [p-fluoro-L-Phe-m-bis-(2-chloroethyl)-amino-L-Phe-Met ethoxy HCl] is a new bifunctional alkylating compound that possesses both cytolytic and antiviral activities. Continuous treatment of mouse mammary tumor cells with 15 microM PTT.119 reduced production of the B-type retrovirus murine mammary tumor virus (MuMTV). MuMTV levels in PTT.119-treated cultures were reduced by 31% in the first 24 hours; an additional 24 hours of treatment resulted in a further reduction of 70%. These reductions were significantly greater than could be accounted for by the effects of PTT.119 tumor cell metabolism and viability. Under identical treatment conditions, equimolar concentrations of L-phenylalanine mustard reduced MuMTV production by only 3%. PTT.119 inhibition of MuMTV replication was also apparent when mammary tumor cells were exposed for periods as short as 0.5-4 hours; persistent decreases in virus production were detected even 7 days following tripeptide treatment. Analyses of the polypeptide composition of MuMTV by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that virions from these PTT.119-treated mammary tumor cultures contained significant reductions in the relative level of the nonglycosylated 24,000-dalton (p24) viral polypeptide associated with the nucleoprotein core. Decreases in p24 were observed in MuMTV produced in the presence of the tripeptide and 1-7 days after removal of PTT.119. Examination of the steady-state levels and rates of intracellular MuMTV protein synthesis suggested that PTT.119 interferes with late steps in MuMTV processing and maturation.

• Authors: M J Yagi, F Maldarelli, S E Chin, J F Holland, J G Bekesi
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 76 Issue 3 Pg. 493-501 (Mar 1986) ISSN: 0027-8874 [Print] United States
• PMID: 3005743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Glycoproteins
• Nitrogen Mustard Compounds
• RNA, Viral
• Retroviridae Proteins
• ambamustine

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (analysis)
• Mammary Tumor Virus, Mouse (drug effects, physiology)
• Mice
• Nitrogen Mustard Compounds (pharmacology, therapeutic use)
• RNA, Viral (biosynthesis)
• Retroviridae (drug effects)
• Retroviridae Proteins (analysis, biosynthesis)
• Virus Replication (drug effects)